We have previously described the receptor mediated uptake of glycoproteins (mannose/N-acetylglucosamine terminal) by alveolar macrophages. In the past year we have demonstrated this receptor to be immunologically related to the hepatic receptor for lysosomal enzymes and expanded our understanding of the kinetics and specificity of uptake. In the coming year I plan to extend these studies and develop a kinetic model for this receptor mediated uptake including the potential role of coated pits and receptor recycling in the endocyclic process. A more detailed understanding of the individual steps of specific endocytosis such as, importance of ligand structure and valency to receptor binding, cell surface clustering of receptor-ligand complexes, discharge of ligand to the lysosome, and redeployment of receptor on the cell surface will greatly enhance our understanding of the regulation of intra- and extracellular distribution of lysosomal enzymes. Many of the techniques for determining the kinetics of the endocytic process are already available in our laboratory and to these I intend to add electron microscopy to study the cellular distribution of receptor and more extensive modification and synthesis in order to study receptor specificity. Recently we have observed that the BANA hydrolase of alveolar macrophages is specifically bound by concanavalin A. I plan to pursue the cellular distribution of this protease in pulmonary tissue and to elucidate if specific macrophage uptake regulates the extracellular levels of this enzyme in pulmonary tissue.